This project is aimed at a comprehensive characterization of the metabolic processes involved in the generation of the cochlear and vestibular endolymphatic potentials and the maintenance of the unique chemical composition of endolymph in different parts of the inner ear. Moreover, the project is concerned with energetic and other aspects of auditory transduction and neural transmission in the oergan of Corti and in vestibular sensory epithelia. Our aims are approached by quantitative biochemical analyses of tissues and fluids by several in vitro techniques and by electrochemical methods in situ under control conditions and during or following various metabolic and/or pharmacological interferences; by comprehensive electrophysiological evaluations during various metabolic interferences, and due to application of investigative drugs or toxic agents applied via the vasculature, perilumph or endolymph; by light and electronmicroscopic evaluations. In fact, in many instances all three basic approaches will be used in combination. The primary experimental animal will be the guinea pig. Because of the complexity of the inner ear very elaborate techniques had to be designed, some of which have already been developed and implemented (e.g. arterial perfusion of the ear with synthetic blood based on artificial oxygen carriers in combination with perilymphatic perfusion; injection of investigative drugs and toxins into endolymph) while others are in various stages of development (e.g. perfusion of scala media without compromising electrical, chemical and morphological indicators of cochlear function). Ultram icrochemical methods used include enzymatic cycling, high performance liquid chromatography, radioimmuno assays and helium glow photometry. Special efforts will be expended to elucidate the specific mode of action of loop dieuretics upon chloride transport. Ultimately, these studies should provide a better understanding of the effects of vascular insufficiency of the ear and shed light upon the biochemical basis of Meniere's disease and the susceptibility to damage by noise and ototoxic drugs.